title: Herniated and spondylotic intervertebral discs of the human cervical spine: histological and immunohistological findings in 500 en bloc surgical samples. Laboratory investigation.
abstract: OBJECTIVE
  In this paper the authors' goal was to identify histological and immunohistochemical differences between cervical disc hemrniation and spondylosis.
  
  
  METHODS
  A total of 500 cervical intervertebral discs were excised from 364 patients: 198 patients with disc herniation and 166 patients with spondylosis. We examined en bloc samples of endplate-ligament-disc complexes. Types of herniation and graded degrees of disc degeneration on MR images were examined histologically and immunohistochemically.
  
  
  RESULTS
  The herniated discs showed granulation tissue, newly developed blood vessels, and massive infiltration of CD68-positive macrophages, which surrounded the herniated tissue mainly in the ruptured outer layer of the anulus fibrosus. The vascular invasion was most significant in uncontained (extruded)-type herniated discs. Chondrocytes positive for matrix metalloproteinase (MMP)-3, tumor necrosis factor (TNF)-alpha, basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF) were abundant in both herniated and spondylotic discs. Free nerve fibers, positive for nerve growth factor (NGF), neurofilament 68, growth-associated protein (GAP)-43, and substance P, were strongly apparent in and around the outer layer of uncontained (extruded)-type herniated discs, with enhanced expression of NGF. The authors observed that herniated discs showed more advanced degeneration in the outer layer of the anulus fibrosus around the granulation tissue than spondylotic discs. On the other hand, spondylotic discs showed more advanced degeneration in the cartilaginous endplate and inner layer of the anulus fibrosus than herniated discs. Spondylotic discs also had thicker bony endplates and expressed TNFalpha and MMP-3 more diffusely than herniated discs, especially in the inner layer of the anulus fibrosus.
  
  
  CONCLUSIONS
  The authors' results indicate that herniated and spondylotic intervertebral discs undergo different degenerative processes. It is likely that TNFa, MMP-3, bFGF, and VEGF expression is upregulated via the herniated mass in the herniated intervertebral discs, but by nutritional impairment in the spondylotic discs. Macrophage accumulation around newly formed blood vessels in the herniated disc tissues seemed to be regulated by MMP-3 and TNFalpha expression, and both herniated and spondylotic discs exhibited marked neoangiogenesis associated with increased bFGF and VEGF expression. Nerve fibers were associated with NGF overexpression in the outer layer of the anulus fibrosus as well as in endothelial cells of the small blood vessels.
authors.affiliation: Department of Orthopaedics and Rehabilitation Medicine, Fukui University Faculty of Medical Sciences, Fukui, Japan. kokubo@u-fukui.ac.jp
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kokubo
authors.forename: Kenzo
authors.initials: K
authors.lastname: Uchida
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yayama
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Sato
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Takaharu
authors.initials: T
authors.lastname: Takamura
authors.forename: Erisa
authors.initials: E
authors.lastname: Mwaka
authors.forename: Norbert
authors.initials: N
authors.lastname: Orwotho
authors.forename: Alexander
authors.initials: A
authors.lastname: Bangirana
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Baba
mesh_terms: D002574:Cervical Vertebrae; D019902:Chondrocytes / Q000737:chemistry / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D019922:GAP-43 Protein / Q000032:analysis; D006097:Granulation Tissue / Q000737:chemistry; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007403:Intervertebral Disc / Q000473:pathology; D007405:Intervertebral Disc Displacement / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D019278:Matrix Metalloproteinase 3 / Q000032:analysis; D009412:Nerve Fibers / Q000737:chemistry; D020932:Nerve Growth Factor / Q000032:analysis; D016900:Neurofilament Proteins / Q000032:analysis; D013128:Spinal Osteophytosis / Q000473:pathology*; D013373:Substance P / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
chemical_list: D019922:GAP-43 Protein; D016900:Neurofilament Proteins; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C066858:neurofilament protein NF 68; D016222:Fibroblast Growth Factor 2; D013373:Substance P; D020932:Nerve Growth Factor; D019278:Matrix Metalloproteinase 3